Despite being the most commonly studied and diagnosed mental disorder in children and adolescents, the exact cause is unknown in the majority of cases.[7] It affects about 5–7% of children when diagnosed via the DSM-IV criteria[8][9] and 1–2% when diagnosed via the ICD-10 criteria.[10] The World Health Organization (WHO) estimated that it affected about 39 million people as of 2013.[11] Rates are similar between countries and depend mostly on how it is diagnosed.[12] ADHD is diagnosed approximately three times more often in boys than in girls, although the disorder is often overlooked in girls due to their symptoms differing from those of boys.[13][14][15] About 30–50% of people diagnosed in childhood continue to have symptoms into adulthood and between 2–5% of adults have the condition.[16][17][18] The condition can be difficult to tell apart from other disorders, as well as to distinguish from high levels of activity that are still within the normal-range.[5]

ADHD management recommendations vary by country and usually involve some combination of counseling, lifestyle changes, and medications.[3] The British guideline only recommends medications as a first-line treatment in children who have severe symptoms and for medication to be considered in those with moderate symptoms who either refuse or fail to improve with counseling, though for adults medications are a first-line treatment.[19] Canadian and American guidelines recommend that medications and behavioral therapy be used together as a first-line therapy, except in preschool-aged children.[20][21] Stimulant medication therapy is not recommended as a first-line therapy in preschool-aged children in either guideline.[19][21] Treatment with stimulants is effective for up to 14 months; however, its long term effectiveness is unclear.[19][22][23][24] Adolescents and adults tend to develop coping skillswhich make up for some or all of their impairments.[25]

The medical literature has described symptoms similar to ADHD since the 19th century.[26] ADHD, its diagnosis, and its treatment have been considered controversial since the 1970s.[27] The controversies have involved clinicians, teachers, policymakers, parents, and the media. Topics include ADHD's causes and the use of stimulant medications in its treatment.[28] Most healthcare providers accept ADHD as a genuine disorder in children and adults, and the debate in the scientific community mainly centers on how it is diagnosed and treated.[29][30][31] The condition was officially known as attention deficit disorder (ADD) from 1980 to 1987 while before this it was known as hyperkinetic reaction of childhood.[32][33]

Inattention, hyperactivity (restlessness in adults), disruptive behavior, and impulsivity are common in ADHD.[34][35] Academic difficulties are frequent as are problems with relationships.[34] The symptoms can be difficult to define as it is hard to draw a line at where normal levels of inattention, hyperactivity, and impulsivity end and significant levels requiring interventions begin.[36]

According to the DSM-5, symptoms must be present for six months or more to a degree that is much greater than others of the same age[9] and they must cause significant problems functioning in at least two settings (e.g., social, school/work, or home).[9] The full criteria must have been met prior to age 12 in order to receive a diagnosis of ADHD.[9]

Have difficulty processing information as quickly and accurately as others

Struggle to follow instructions

Have trouble understanding minute details

A child with ADHD hyperactive/impulsive type has most or all of the following symptoms, excluding situations where these symptoms are better explained by another psychiatric or medical condition:[9][37]

Fidget and squirm in their seats

Talk nonstop

Dash around, touching or playing with anything and everything in sight

Have trouble sitting still during dinner, school, doing homework, and story time

Be constantly in motion

Have difficulty doing quiet tasks or activities

Be very impatient

Blurt out inappropriate comments, show their emotions without restraint, and act without regard for consequences

Have difficulty waiting for things they want or waiting their turns in games

Often interrupt conversations or others' activities

Symptoms of hyperactivity tend to go away with age and turn into "inner restlessness" in teens and adults with ADHD.[16]

People with ADHD of all ages are more likely to have problems with social skills, such as social interaction and forming and maintaining friendships. This is true for all subtypes. About half of children and adolescents with ADHD experience social rejection by their peers compared to 10–15% of non-ADHD children and adolescents. People with attention deficits are prone to having difficulty processing verbal and nonverbal language which can negatively affect social interaction. They also may drift off during conversations, and miss social cues.[38]

Difficulties managing anger are more common in children with ADHD[39] as are poor handwriting[40] and delays in speech, language and motor development.[41][42] Although it causes significant impairment, particularly in modern society, many children with ADHD have a good attention span for tasks they find interesting.[6]

In children, ADHD occurs with other disorders about ⅔ of the time.[6] Some commonly associated conditions include:

Learning disabilities have been found to occur in about 20–30% of children with ADHD. Learning disabilities can include developmental speech and language disorders and academic skills disorders.[43] ADHD, however, is not considered a learning disability, but it very frequently causes academic difficulties.[43]

Primary disorder of vigilance, which is characterized by poor attention and concentration, as well as difficulties staying awake. These children tend to fidget, yawn and stretch and appear to be hyperactive in order to remain alert and active.[45]

Substance use disorders. Adolescents and adults with ADHD are at increased risk of substance abuse.[16] This is most commonly seen with alcohol or cannabis.[16] The reason for this may be an altered reward pathway in the brains of ADHD individuals.[16] This makes the evaluation and treatment of ADHD more difficult, with serious substance misuse problems usually treated first due to their greater risks.[19][50]

Sleep disorders and ADHD commonly co-exist. They can also occur as a side effect of medications used to treat ADHD. In children with ADHD, insomnia is the most common sleep disorder with behavioral therapy the preferred treatment.[54][55] Problems with sleep initiation are common among individuals with ADHD but often they will be deep sleepers and have significant difficulty getting up in the morning.[56]Melatonin is sometimes used in children who have sleep onset insomnia.[57]

A 2016 systematic review found a well established association between ADHD and obesity, asthma and sleep disorders, and tentative evidence for association with celiac disease and migraine,[59] while another 2016 systematic review did not support a clear link between celiac disease and ADHD, and stated that routine screening for celiac disease in people with ADHD is discouraged.[60]

Overall, studies have shown that people with ADHD tend to have lower scores on intelligence quotient (IQ) tests.[61] The significance of this is controversial due to the differences between people with ADHD and the difficulty determining the influence of symptoms, such as distractibility, on lower scores rather than intellectual capacity.[61] In studies of ADHD, higher IQs may be over represented because many studies exclude individuals who have lower IQs despite those with ADHD scoring on average 9 points lower on standardized intelligence measures.[62]

The cause of most cases of ADHD is unknown; however, it is believed to involve interactions between genetic and environmental factors.[63][64] Certain cases are related to previous infection of or trauma to the brain.[63]

Twin studies indicate that the disorder is often inherited from one's parents with genetics determining about 75% of cases.[19][65][66] Siblings of children with ADHD are three to four times more likely to develop the disorder than siblings of children without the disorder.[67] Genetic factors are also believed to be involved in determining whether ADHD persists into adulthood.[68]

Evolution may have played a role in the high rates of ADHD, particularly hyperactive and impulsive traits in males.[75] Some have hypothesized that some women may be more attracted to males who are risk takers, increasing the frequency of genes that predispose to hyperactivity and impulsivity in the gene pool.[76] Others have claimed that these traits may be an adaptation that helped males face stressful or dangerous environment with, for example, increased impulsivity and exploratory behavior.[75][76] In certain situations, ADHD traits may have been beneficial to society as a whole even while being harmful to the individual.[75][76][77] The high rates and heterogeneity of ADHD may have increased reproductive fitness and benefited society by adding diversity to the gene pool despite being detrimental to the individual.[77] In certain environments, some ADHD traits may have offered personal advantages to individuals, such as quicker response to predators or superior hunting skills.[78]

Some studies suggest that in a minority of children, artificial food dyes or preservative may be associated with an increased prevalence of ADHD or ADHD-like symptoms[7][89] but the evidence is weak and may only apply to children with food sensitivities.[89][90][91] The United Kingdom and the European Union have put in place regulatory measures based on these concerns.[92] In a minority of children, intolerances or allergies to certain foods may worsen ADHD symptoms.[93]

Research does not support popular beliefs that ADHD is caused by eating too much refined sugar, watching too much television, parenting, poverty or family chaos; however, they might worsen ADHD symptoms in certain people.[35]

The diagnosis of ADHD can represent family dysfunction or a poor educational system rather than an individual problem.[94] Some cases may be explained by increasing academic expectations, with a diagnosis being a method for parents in some countries to get extra financial and educational support for their child.[88] The youngest children in a class have been found to be more likely to be diagnosed as having ADHD possibly due to their being developmentally behind their older classmates.[95][96] Behaviors typical of ADHD occurs more commonly in children who have experienced violence and emotional abuse.[19]

The social construct theory of ADHD suggests that because the boundaries between "normal" and "abnormal" behavior are socially constructed, i.e. jointly created and validated by all members of society, and in particular by physicians, parents, and teachers, it then follows that subjective valuations and judgements determine which diagnostic criteria are used and, thus, the number of people affected.[97] This could lead to the situation where the DSM-IV arrives at levels of ADHD three to four times higher than those obtained with the ICD-10.[15]Thomas Szasz, a supporter of this theory, has argued that ADHD was "invented and not discovered."[98][99]

In children with ADHD, there is a general reduction of volume in certain brain structures, with a proportionally greater decrease in the volume in the left-sided prefrontal cortex.[101][105] The posterior parietal cortex also shows thinning in ADHD individuals compared to controls.[101] Other brain structures in the prefrontal-striatal-cerebellar and prefrontal-striatal-thalamic circuits have also been found to differ between people with and without ADHD.[101][103][104]

The symptoms of ADHD arise from a deficiency in certain executive functions (e.g., attentional control, inhibitory control, and working memory).[56][101][102][110] Executive functions are a set of cognitive processes that are required to successfully select and monitor behaviors that facilitate the attainment of one's chosen goals.[56][102][110] The executive function impairments that occur in ADHD individuals result in problems with staying organized, time keeping, excessive procrastination, maintaining concentration, paying attention, ignoring distractions, regulating emotions, and remembering details.[56][101][102] People with ADHD appear to have unimpaired long-term memory, and deficits in long-term recall appear to be attributed to impairments in working memory.[56][111] The criteria for an executive function deficit are met in 30–50% of children and adolescents with ADHD.[112] One study found that 80% of individuals with ADHD were impaired in at least one executive function task, compared to 50% for individuals without ADHD.[113] Due to the rates of brain maturation and the increasing demands for executive control as a person gets older, ADHD impairments may not fully manifest themselves until adolescence or even early adulthood.[56]

ADHD has also been associated with motivational deficits in children.[114] Children with ADHD find it difficult to focus on long-term over short-term rewards, and exhibit impulsive behavior for short-term rewards.[114]

ADHD is diagnosed by an assessment of a person's childhood behavioral and mental development, including ruling out the effects of drugs, medications and other medical or psychiatric problems as explanations for the symptoms.[19] It often takes into account feedback from parents and teachers[5] with most diagnoses begun after a teacher raises concerns.[88] It may be viewed as the extreme end of one or more continuous human traits found in all people.[19] Whether someone responds to medications does not confirm or rule out the diagnosis. As imaging studies of the brain do not give consistent results between individuals, they are only used for research purposes and not diagnosis.[115]

Associated conditions that should be screened for include anxiety, depression, oppositional defiant disorder, conduct disorder, and learning and language disorders. Other conditions that should be considered are other neurodevelopmental disorders, tics, and sleep apnea.[117]

As with many other psychiatric disorders, formal diagnosis should be made by a qualified professional based on a set number of criteria. In the United States, these criteria are defined by the American Psychiatric Association in the DSM. Based on the DSM criteria, there are three sub-types of ADHD:[9]

This subdivision is based on presence of at least six out of nine long-term (lasting at least six months) symptoms of inattention, hyperactivity–impulsivity, or both.[122] To be considered, the symptoms must have appeared by the age of six to twelve and occur in more than one environment (e.g. at home and at school or work).[4] The symptoms must be not appropriate for a child of that age[4][123] and there must be evidence that it is causing social, school or work related problems.[122]

In the ICD-10, the symptoms of "hyperkinetic disorder" are analogous to ADHD in the DSM-5. When a conduct disorder (as defined by ICD-10)[41] is present, the condition is referred to as hyperkinetic conduct disorder. Otherwise, the disorder is classified as disturbance of activity and attention, other hyperkinetic disorders or hyperkinetic disorders, unspecified. The latter is sometimes referred to as hyperkinetic syndrome.[41]

In the preliminary draft for ICD-11 (planned for 2018), ADHD is classified under 6A42 (Attention deficit hyperactivity disorder) and everything seems to be fully identical now to DSM-5.[124]

Adults with ADHD are diagnosed under the same criteria, including that their signs must have been present by the age of six to twelve. Questioning parents or guardians as to how the person behaved and developed as a child may form part of the assessment; a family history of ADHD also adds weight to a diagnosis.[16] While the core symptoms of ADHD are similar in children and adults they often present differently in adults than in children, for example excessive physical activity seen in children may present as feelings of restlessness and constant mental activity in adults.[16]

It is estimated that between 2–5% of adults have ADHD.[16] Around 25-50% of children with ADHD continue to experience ADHD symptoms into adulthood, while the rest experiences fewer or no symptoms.[9][16] Currently, most adults remain untreated.[125] Many adults with ADHD without diagnosis and treatment have a disorganized life and some use non-prescribed drugs or alcohol as a coping mechanism.[25] Other problems may include relationship and job difficulties, and an increased risk of criminal activities.[16] Associated mental health problems include: depression, anxiety disorder, and learning disabilities.[25]

Some ADHD symptoms in adults differ from those seen in children. While children with ADHD may climb and run about excessively, adults may experience an inability to relax, or they talk excessively in social situations. Adults with ADHD may start relationships impulsively, display sensation-seeking behavior, and be short-tempered. Addictive behavior such as substance abuse and gambling are common. The DSM-V criteria do specifically deal with adults, unlike those in DSM-IV, which were criticized for not being appropriate for adults; those who presented differently may lead to the claim that they outgrew the diagnosis.[16]

Primary sleep disorders may affect attention and behavior and the symptoms of ADHD may affect sleep.[127] It is thus recommended that children with ADHD be regularly assessed for sleep problems.[128] Sleepiness in children may result in symptoms ranging from the classic ones of yawning and rubbing the eyes, to hyperactivity and inattentiveness.[129]Obstructive sleep apnea can also cause ADHD type symptoms.[129]

Reviews of ADHD biomarkers have noted that platelet monoamine oxidase expression, urinary norepinephrine, urinary MHPG, and urinary phenethylamine levels consistently differ between ADHD individuals and healthy control.[130][131] These measurements could potentially serve as diagnostic biomarkers for ADHD, but more research is needed to establish their diagnostic utility.[131] Urinary and blood plasma phenethylamine concentrations are lower in ADHD individuals relative to controls and the two most commonly prescribed drugs for ADHD, amphetamine and methylphenidate, increase phenethylamine biosynthesis in treatment-responsive individuals with ADHD.[130][131][71] Lower urinary phenethylamine concentrations are also associated with symptoms of inattentiveness in ADHD individuals.[131]

The management of ADHD typically involves counseling or medications either alone or in combination. While treatment may improve long-term outcomes, it does not get rid of negative outcomes entirely.[132] Medications used include stimulants, atomoxetine, alpha-2 adrenergic receptor agonists, and sometimes antidepressants.[48][107] In those who have trouble focussing on long-term rewards, a large amount of positive reinforcement improves task performance.[114] ADHD stimulants also improve persistence and task performance in children with ADHD.[101][114]

Parent training and education have been found to have short-term benefits.[138][139] There is little high quality research on the effectiveness of family therapy for ADHD, but the evidence that exists shows that it is similar to community care and better than a placebo.[140] Several ADHD specific support groups exist as informational sources and may help families cope with ADHD.[141]

Training in social skills, behavioral modification and medication may have some limited beneficial effects. The most important factor in reducing later psychological problems, such as major depression, criminality, school failure, and substance use disorders is formation of friendships with people who are not involved in delinquent activities.[142]

Regular physical exercise, particularly aerobic exercise, is an effective add-on treatment for ADHD in children and adults, particularly when combined with stimulant medication, although the best intensity and type of aerobic exercise for improving symptoms are not currently known.[143][144][145] In particular, the long-term effects of regular aerobic exercise in ADHD individuals include better behavior and motor abilities, improved executive functions (including attention, inhibitory control, and planning, among other cognitive domains), faster information processing speed, and better memory.[143][144][145] Parent-teacher ratings of behavioral and socio-emotional outcomes in response to regular aerobic exercise include: better overall function, reduced ADHD symptoms, better self-esteem, reduced levels of anxiety and depression, fewer somatic complaints, better academic and classroom behavior, and improved social behavior.[143] Exercising while on stimulant medication augments the effect of stimulant medication on executive function.[143] It is believed that these short-term effects of exercise are mediated by an increased abundance of synaptic dopamine and norepinephrine in the brain.[143]

Stimulant medications are the pharmaceutical treatment of choice.[146][147] They have at least some effect on symptoms in the short term in about 80% of people.[24]Methylphenidate appears to improve symptoms as reported by teachers and parents.[148] Stimulants may also reduce the risk of injuries in children with ADHD.[149]

There are a number of non-stimulant medications, such as atomoxetine, bupropion, guanfacine, and clonidine that may be used as alternatives, or added to stimulant therapy.[146][150] There are no good studies comparing the various medications; however, they appear more or less equal with respect to side effects.[151] Stimulants appear to improve academic performance while atomoxetine does not.[152] Atomoxetine, due to its lack of addiction liability, may be preferred in those who are at risk of recreational or compulsive stimulant use.[16] There is little evidence on the effects of medication on social behaviors.[151] As of June 2015[update], the long-term effects of ADHD medication have yet to be fully determined.[153][154]Magnetic resonance imaging studies suggest that long-term treatment with amphetamine or methylphenidate decreases abnormalities in brain structure and function found in subjects with ADHD.[155][156][157]

Guidelines on when to use medications vary by country, with the United Kingdom's National Institute for Health and Care Excellence recommending use for children only in severe cases, though for adults medication is a first-line treatment, while most United States guidelines recommend medications in most age groups.[20] Medications are not recommended for preschool children.[19][158] Underdosing of stimulants may occur and result in a lack of response or later loss of effectiveness.[159] This is particularly common in adolescents and adults as approved dosing is based on school-aged children, causing some practitioners to use weight based or benefit based off-label dosing instead.[160][161][162]

While stimulants and atomoxetine are usually safe, there are side-effects and contraindications to their use.[146] A large overdose on ADHD stimulants is commonly associated with symptoms such as stimulant psychosis and mania;[163] although very rare, at therapeutic doses these events appear to occur in approximately 0.1% of individuals within the first several weeks after starting amphetamine or methylphenidate therapy.[164][163][165] Administration of an antipsychotic medication has been found to effectively resolve the symptoms of acute amphetamine psychosis.[163] Regular monitoring has been recommended in those on long-term treatment.[166] Stimulant therapy should be stopped periodically to assess continuing need for medication, decrease possible growth delay, and reduce tolerance.[167][168] Long-term misuse of stimulant medications at doses above the therapeutic range for ADHD treatment is associated with addiction and dependence.[169][170] Untreated ADHD, however, is also associated with elevated risk of substance use disorders and conduct disorders.[169] The use of stimulants appears to either reduce this risk or have no effect on it.[16][153][169] The safety of these medications in pregnancy is unclear.[171]

Dietary modifications may be of benefit to a small proportion of children with ADHD.[172] A 2013 meta-analysis found less than a third of children with ADHD see some improvement in symptoms with free fatty acid supplementation or decreased eating of artificial food coloring.[90] These benefits may be limited to children with food sensitivities or those who are simultaneously being treated with ADHD medications.[90] This review also found that evidence does not support removing other foods from the diet to treat ADHD.[90] A 2014 review found that an elimination diet results in a small overall benefit.[93] A 2016 review stated that the use of a gluten-free diet as standard ADHD treatment is discouraged.[60] Iron, magnesium and iodine may also have an effect on ADHD symptoms.[173] There is a small amount of evidence that lower tissue zinc levels may be associated with ADHD.[174] In the absence of a demonstrated zinc deficiency (which is rare outside of developing countries), zinc supplementation is not recommended as treatment for ADHD.[175] However, zinc supplementation may reduce the minimum effective dose of amphetamine when it is used with amphetamine for the treatment of ADHD.[176] There is evidence of a modest benefit of omega 3 fatty acid supplementation, but it is not recommended in place of traditional medication.[177][178]

An 8-year follow up of children diagnosed with ADHD (combined type) found that they often have difficulties in adolescence, regardless of treatment or lack thereof.[179] In the USA, fewer than 5% of individuals with ADHD get a college degree,[180] compared to 28% of the general population aged 25 years and older.[181] The proportion of children meeting criteria for ADHD drops by about half in the three years following the diagnosis and this occurs regardless of treatments used.[182][183] ADHD persists into adulthood in about 30–50% of cases.[17] Those affected are likely to develop coping mechanisms as they mature, thus compensating to some extent for their previous symptoms.[25]

ADHD is estimated to affect about 6–7% of people aged 18 and under when diagnosed via the DSM-IV criteria.[8] When diagnosed via the ICD-10 criteria rates in this age group are estimated at 1–2%.[10] Children in North America appear to have a higher rate of ADHD than children in Africa and the Middle East; this is believed to be due to differing methods of diagnosis rather than a difference in underlying frequency.[184] If the same diagnostic methods are used, the rates are more or less the same between countries.[12] It is diagnosed approximately three times more often in boys than in girls.[14][15] This difference between sexes may reflect either a difference in susceptibility or that females with ADHD are less likely to be diagnosed than males.[185]

Rates of diagnosis and treatment have increased in both the United Kingdom and the United States since the 1970s.[186] This is believed to be primarily due to changes in how the condition is diagnosed[186] and how readily people are willing to treat it with medications rather than a true change in how common the condition is.[10] It is believed that changes to the diagnostic criteria in 2013 with the release of the DSM-5 will increase the percentage of people diagnosed with ADHD, especially among adults.[187]

Hyperactivity has long been part of the human condition. Sir Alexander Crichton describes "mental restlessness" in his book An inquiry into the nature and origin of mental derangement written in 1798.[188][189] ADHD was first clearly described by George Still in 1902.[186]

The terminology used to describe the condition has changed over time and has included: in the DSM-I (1952) "minimal brain dysfunction", in the DSM-II (1968) "hyperkinetic reaction of childhood", in the DSM-III (1980) "attention-deficit disorder (ADD) with or without hyperactivity".[186] In 1987 this was changed to ADHD in the DSM-III-R and the DSM-IV in 1994 split the diagnosis into three subtypes, ADHD inattentive type, ADHD hyperactive-impulsive type and ADHD combined type.[190] These terms were kept in the DSM-5 in 2013.[9] Other terms have included "minimal brain damage" used in the 1930s.[191]

The use of stimulants to treat ADHD was first described in 1937.[192] In 1934, Benzedrine became the first amphetamine medication approved for use in the United States.[193] Methylphenidate was introduced in the 1950s, and enantiopure dextroamphetamine in the 1970s.[186]

ADHD, its diagnosis, and its treatment have been controversial since the 1970s.[27][28][194] The controversies involve clinicians, teachers, policymakers, parents, and the media. Positions range from the view that ADHD is within the normal range of behavior[19][195] to the hypothesis that ADHD is a genetic condition.[196] Other areas of controversy include the use of stimulant medications in children,[28][197] the method of diagnosis, and the possibility of overdiagnosis.[197] In 2012, the National Institute for Health and Care Excellence, while acknowledging the controversy, states that the current treatments and methods of diagnosis are based on the dominant view of the academic literature.[19] In 2014, Keith Conners, one of the early advocates for recognition of the disorder, spoke out against overdiagnosis in a New York Times article.[198] In contrast, a 2014 peer-reviewed medical literature review indicated that ADHD is underdiagnosed in adults.[18]

With widely differing rates of diagnosis across countries, states within countries, races, and ethnicities, some suspect factors other than the presence of the symptoms of ADHD are playing a role in diagnosis.[95] Some sociologists consider ADHD to be an example of the medicalization of deviant behavior, that is, the turning of the previously non-medical issue of school performance into a medical one.[27][88] Most healthcare providers accept ADHD as a genuine disorder, at least in the small number of people with severe symptoms.[88] Among healthcare providers the debate mainly centers on diagnosis and treatment in the much greater number of people with less severe symptoms.[30][31][88]

As of 2009[update], 8% of all United States Major League Baseball players had been diagnosed with ADHD, making the disorder common among this population. The increase coincided with the League's 2006 ban on stimulants, which has raised concern that some players are mimicking or falsifying the symptoms or history of ADHD to get around the ban on the use of stimulants in sport.[199]

A number of public figures have given controversial statements regarding ADHD. Tom Cruise has described the medications Ritalin (methylphenidate) and Adderall (a mixed-salt amphetamine formulation) as "street drugs".[200] Ushma S. Neill criticized this view, stating that the doses of stimulants used in the treatment of ADHD do not cause addiction and that there is some evidence of a reduced risk of later substance addiction in children treated with stimulants.[201] In the UK, Susan Greenfield spoke out publicly in 2007 in the House of Lords about the need for a wide-ranging inquiry into the dramatic increase in the diagnosis of ADHD, and possible causes. Her comments followed a BBCPanorama program that highlighted research that suggested medications are no better than other forms of therapy in the long term.[202] In 2010, the BBC Trust criticized the 2007 Panorama program for summarizing the research as showing "no demonstrable improvement in children's behaviour after staying on ADHD medication for three years" when in actuality "the study found that medication did offer a significant improvement over time" although the long-term benefits of medication were found to be "no better than children who were treated with behavior therapy."[203]

^ abcErtürk, E; Wouters, S; Imeraj, L; Lampo, A (29 January 2016). "Association of ADHD and Celiac Disease: What Is the Evidence? A Systematic Review of the Literature.". Journal of Attention Disorders (Review). doi:10.1177/1087054715611493. PMID26825336. Up till now, there is no conclusive evidence for a relationship between ADHD and CD. Therefore, it is not advised to perform routine screening of CD when assessing ADHD (and vice versa) or to implement GFD as a standard treatment in ADHD. Nevertheless, the possibility of untreated CD predisposing to ADHD-like behavior should be kept in mind. ... It is possible that in untreated patients with CD, neurologic symptoms such as chronic fatigue, inattention, pain, and headache could predispose patients to ADHD-like behavior (mainly symptoms of inattentive type), which may be alleviated after GFD treatment. (CD: celiac disease; GFD: gluten-free diet)

^ abBerry, MD (January 2007). "The potential of trace amines and their receptors for treating neurological and psychiatric diseases". Reviews on Recent Clinical Trials. 2 (1): 3–19. doi:10.2174/157488707779318107. PMID18473983. Although there is little direct evidence, changes in trace amines, in particular PE, have been identified as a possible factor for the onset of attention deficit/hyperactivity disorder (ADHD). … Further, amphetamines, which have clinical utility in ADHD, are good ligands at trace amine receptors. Of possible relevance in this aspect is modafanil, which has shown beneficial effects in ADHD patients and has been reported to enhance the activity of PE at TAAR1. Conversely, methylphenidate, …showed poor efficacy at the TAAR1 receptor. In this respect it is worth noting that the enhancement of functioning at TAAR1 seen with modafanil was not a result of a direct interaction with TAAR1.

^ abcdefghMalenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 148, 154–157. ISBN9780071481274. DA has multiple actions in the prefrontal cortex. It promotes the "cognitive control" of behavior: the selection and successful monitoring of behavior to facilitate attainment of chosen goals. Aspects of cognitive control in which DA plays a role include working memory, the ability to hold information "on line" in order to guide actions, suppression of prepotent behaviors that compete with goal-directed actions, and control of attention and thus the ability to overcome distractions. Cognitive control is impaired in several disorders, including attention deficit hyperactivity disorder. ... Noradrenergic projections from the LC thus interact with dopaminergic projections from the VTA to regulate cognitive control. ... it has not been shown that 5HT makes a therapeutic contribution to treatment of ADHD.NOTE: DA: dopamine, LC: locus coeruleus, VTA: ventral tegmental area, 5HT: serotonin (5-hydroxytryptamine)

^ abcdModesto-Lowe V, Chaplin M, Soovajian V, Meyer A (2013). "Are motivation deficits underestimated in patients with ADHD? A review of the literature". Postgrad Med. 125 (4): 47–52. doi:10.3810/pgm.2013.07.2677. PMID23933893. Behavioral studies show altered processing of reinforcement and incentives in children with ADHD. These children respond more impulsively to rewards and choose small, immediate rewards over larger, delayed incentives. Interestingly, a high intensity of reinforcement is effective in improving task performance in children with ADHD. Pharmacotherapy may also improve task persistence in these children. ... Previous studies suggest that a clinical approach using interventions to improve motivational processes in patients with ADHD may improve outcomes as children with ADHD transition into adolescence and adulthood.

^ abKiely B, Adesman A (June 2015). "What we do not know about ADHD… yet". Curr. Opin. Pediatr. 27 (3): 395–404. doi:10.1097/MOP.0000000000000229. PMID25888152. In addition, a consensus has not been reached on the optimal diagnostic criteria for ADHD. Moreover, the benefits and long-term effects of medical and complementary therapies for this disorder continue to be debated. These gaps in knowledge hinder the ability of clinicians to effectively recognize and treat ADHD.

^Frodl T, Skokauskas N (February 2012). "Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand. 125 (2): 114–126. doi:10.1111/j.1600-0447.2011.01786.x. PMID22118249. Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure.

^Biederman, Joseph (2003). "New-Generation Long-Acting Stimulants for the Treatment of Attention-Deficit/Hyperactivity Disorder". Medscape. Retrieved 19 June 2016. As most treatment guidelines and prescribing information for stimulant medications relate to experience in school-aged children, prescribed doses for older patients are lacking. Emerging evidence for both methylphenidate and Adderall indicate that when weight-corrected daily doses, equipotent with those used in the treatment of younger patients, are used to treat adults with ADHD, these patients show a very robust clinical response consistent with that observed in pediatric studies. These data suggest that older patients may require a more aggressive approach in terms of dosing, based on the same target dosage ranges that have already been established -- for methylphenidate, 1-1.5-2 mg/kg/day, and for D,L-amphetamine, 0.5-0.75-1 mg/kg/day....
In particular, adolescents and adults are vulnerable to underdosing, and are thus at potential risk of failing to receive adequate dosage levels. As with all therapeutic agents, the efficacy and safety of stimulant medications should always guide prescribing behavior: careful dosage titration of the selected stimulant product should help to ensure that each patient with ADHD receives an adequate dose, so that the clinical benefits of therapy can be fully attained.

^ abcShoptaw SJ, Kao U, Ling W (January 2009). Shoptaw SJ, Ali R, ed. "Treatment for amphetamine psychosis". Cochrane Database Syst. Rev. (1): CD003026. doi:10.1002/14651858.CD003026.pub3. PMID19160215. A minority of individuals who use amphetamines develop full-blown psychosis requiring care at emergency departments or psychiatric hospitals. In such cases, symptoms of amphetamine psychosis commonly include paranoid and persecutory delusions as well as auditory and visual hallucinations in the presence of extreme agitation. More common (about 18%) is for frequent amphetamine users to report psychotic symptoms that are sub-clinical and that do not require high-intensity intervention ...
About 5–15% of the users who develop an amphetamine psychosis fail to recover completely (Hofmann 1983) ...
Findings from one trial indicate use of antipsychotic medications effectively resolves symptoms of acute amphetamine psychosis.

^"Adderall XR Prescribing Information"(PDF). United States Food and Drug Administration. Shire US Inc. December 2013. Retrieved 30 December 2013. Treatment-emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without prior history of psychotic illness or mania can be caused by stimulants at usual doses. ... In a pooled analysis of multiple short-term, placebo controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.

^Krause J (April 2008). "SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder". Expert Rev. Neurother. 8 (4): 611–625. doi:10.1586/14737175.8.4.611. PMID18416663. Zinc binds at ... extracellular sites of the DAT [103], serving as a DAT inhibitor. In this context, controlled double-blind studies in children are of interest, which showed positive effects of zinc [supplementation] on symptoms of ADHD [105,106]. It should be stated that at this time [supplementation] with zinc is not integrated in any ADHD treatment algorithm.